Pregnancy loss and risk of multiple sclerosis and autoimmune neurological disorder: A nationwide cohort study.

BACKGROUND

The loss of one or more pregnancies before viability (i.e. pregnancy loss or miscarriage), has been linked to an increased risk of diseases later in life such as myocardial infarction and stroke. Recurrent pregnancy loss (i.e. three consecutive pregnancy losses) and multiple sclerosis have both been linked to immunological traits, which could predispose to both occurrences. The objective of the current study was to investigate if pregnancy loss is associated with later autoimmune neurological disease.

METHODS

This register-based cohort study, included the Danish female population age 12 or older between 1977-2017. Women were grouped hierarchically: 0, 1, 2, ≥3 pregnancy losses, primary recurrent pregnancy loss (i.e. not preceded by a delivery), and secondary recurrent pregnancy loss (i.e. preceded by a delivery). The main outcome was multiple sclerosis and additional outcomes were amyotrophic lateral sclerosis, Guillain-Barré syndrome, and myasthenia gravis. Bayesian Poisson regression estimated incidence rate ratios [IRR] and 95% credible intervals [CI] adjusted for year, age, live births, family history of an outcome, and education.

RESULTS

After 40,380,194 years of follow-up, multiple sclerosis was diagnosed among 7,667 out of 1,513,544 included women (0.5%), median age at diagnosis 34.2 years (IQR 27.4-41.4 years), and median age at symptom onset 31.2 years (IQR 24.8-38.2). The adjusted IRR of multiple sclerosis after 1 pregnancy loss was: 1.03 (95% CI 0.95-1.11), 2 losses: 1.02 (95% CI 0.86-1.20), ≥3 non-consecutive losses: 0.81 (95% CI 0.51-1.24), primary recurrent pregnancy loss: 1.18 (95% CI 0.84-1.60), secondary recurrent pregnancy loss: 1.16 (95% CI 0.81-1.63), as compared to women with no pregnancy losses. Seven sensitivity analyses and analyses for additional outcomes did not show significantly elevated adjusted risk estimates.

CONCLUSIONS

In this nationwide study, pregnancy loss was not significantly associated with autoimmune neurological disorder.

Déclaration de conflit d'intérêts

Amended Competing Interests statement: The authors report no conflicts of interest for the current study. For funding of research not relating to the current study, authors report: HSN received research grants from commercial sources: Freya Biosciences ApS, Ferring Pharmaceuticals, BioInnovation Institute, and non-commercial sources: Novo Nordisk Foundation, Ministry of Education, Augustinus Foundation, and Oda and Hans Svenningsens Foundation. For funding of research not relating to the current study DW reports a research grant from non-commercial source: Novo Nordisk Foundation. For work not relating to the current study HSN reports honoraria for lectures (speakers-fee) from commercial sources: Ferring Pharmaceuticals, Merck A/S, Astra Zenica, and Cook Medical. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No authors report employment, consultancy, patents, or work relating to products in development, or marketed products. This does not alter our adherence to PLOS ONE policies on sharing data and materials.